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Brief summary The Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of XmAb942 in healthy volunteers (Parts A and B). Part C of this study will be a Phase 2 study to evaluate XmAb942 in participants with ulcerative colitis (UC).
This study consists of 3 parts, as follows:
Part A: Single ascending dose (SAD) in healthy participants, will entail administration of XmAb942 or matching placebo at 3 different dose levels of XmAb942.
Part B: Repeat dosing for up to 3 doses, will entail administration of XmAb942 or matching placebo at 2 different dose levels of XmAb942.
Part C: Participants with moderately to severely active UC to receive 3 different dose levels of XmAb942 or placebo during a 12-week induction period and single dose level of XmAb942 during a 40-week maintenance period, followed by a 24 week follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Active drug | Active Comparator | Active XmAb942 to be administered to healthy volunteers. Single administration of 3 ascending dose (SAD) levels of XmAb942 via SC (3 cohorts) or IV (3 cohorts) administration in 8 participants per cohort, randomized in a 3:1 ratio to active or placebo. |
|
| Part A: Placebo | Placebo Comparator | Placebo Comparator to be administered to healthy volunteers. Single administration of 3 ascending dose (SAD) levels will be randomized in a 3:1 ratio to active or placebo. |
|
| Part B: Active | Active Comparator | Active XmAb942 to be administered to healthy volunteers. Multiple administrations of 2 ascending dose (MAD) levels of XmAb942 via IV administration in 8 participants per cohort, randomized in a 3:1 ratio to active or placebo. |
|
| Part B: Placebo | Placebo Comparator | Placebo Comparator to be administered to healthy volunteers. Multiple administrations of 2 ascending dose (MAD) levels will be randomized in a 3:1 ratio to active or placebo. |
|
| Part C: Active | Active Comparator | Active XmAb942 to be administered to participants with moderately to severely active Ulcerative Colitis |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XmAb942 | Biological | Antibody |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A) | 20 weeks | |
| Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part B) | 28 weeks | |
| Clinical remission based on modified mayo score (MMS), defined as MMS ≤ 2 with Mayo endoscopic score (MES) of 1, rectal bleeding subscore (RBS) of 0, and stool frequency subscore (SFS) of 0-1. | A composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9. It is calculated by adding the results from Mayo endoscopic subscore (MES) which measures GI bleeding, stool frequency subscore (SFS) which measures stool frequency per day, and rectal bleeding subscore (RBS), which measures presence of blood during stool passing. Each subscore is a scale of increasing severity from 0 to 3. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part A) | • Cmax (Maximum concentration of drug) | up to 20 weeks |
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part A) | • AUC0-last (Area under the curve drug concentration-time curve to last concentration) |
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Inclusion Criteria:
Parts A and B
Part C
Exclusion Criteria:
Parts A and B
Part C
Other protocol defined inclusion/exclusion criteria apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sudeepta Aggarwal | Contact | Xenith-UCinfo@xencor.com | ||
| Mark Osterman, MD, MSCE | Contact | Xenith-UCinfo@xencor.com |
| Name | Affiliation | Role |
|---|---|---|
| Mark Osterman, MD, MSCE | Xencor, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xencor Investigative Site | Recruiting | Scottsdale | Arizona | 85255 | United States | |
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|
| Part C: placebo | Placebo Comparator | Placebo comparator to be administered to participants with moderately to severely active Ulcerative Colitis |
|
| Placebo | Drug | Placebo |
|
| up to 20 weeks |
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part B) | • Cmax (Maximum concentration of drug) | up to 28 weeks |
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part B) | • AUC0-tau AUC within a dosing interval, calculated using the linear trapezoidal rule | up to 28 weeks |
| Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) (Part C) | 72 weeks |
| Discontinuations due to TEAEs (Part C) | 72 weeks |
| Endoscopic improvement defined as (MES) of 0 or 1 (Part C). | 12 weeks |
| Change from baseline in MS (Part C). | 12 weeks |
| Clinical response based on MMS score (Part C) defined as decrease from baseline in the MMS of ≥ 2 points and at least a 30% reduction from baseline, and decrease of ≥ 1 point in RBS from baseline or absolute RBS ≤ 1 | 12 weeks |
| Histological improvement as determined by change in Robarts Histopathology Index (RHI) scores, ranging from 0 (no disease activity) to 33 (severe disease activity). | 12 weeks |
| Xencor Investigative Site |
| Recruiting |
| Bradenton |
| Florida |
| 34209 |
| United States |
| Xencor Investigative Site | Recruiting | Brandon | Florida | 33511 | United States |
| Xencor Investigative Site | Recruiting | Jacksonville | Florida | 32258 | United States |
| Xencor Investigative Site | Recruiting | Kissimmee | Florida | 34741 | United States |
| Xencor Investigative Site | Recruiting | Margate | Florida | 33063 | United States |
| Xencor Investigative Site | Recruiting | Palmetto Bay | Florida | 33176 | United States |
| Xencor Investigative Site | Recruiting | Tampa | Florida | 33613 | United States |
| Xencor Investigative Site | Recruiting | Louisville | Kentucky | 40218 | United States |
| Xencor Investigative Site | Recruiting | Albany | New York | 12206 | United States |
| Xencor Investigative Site | Recruiting | Rochester | New York | 14618 | United States |
| Xencor Investigative Site | Recruiting | Raleigh | North Carolina | 27612 | United States |
| Xencor Investigative Site | Recruiting | Beavercreek | Ohio | 45440 | United States |
| Xencor Investigative Site | Recruiting | Cedar Park | Texas | 78613 | United States |
| Xencor Investigative Site | Recruiting | Denton | Texas | 76201 | United States |
| Xencor Investigative Site | Recruiting | Georgetown | Texas | 78628 | United States |
| Xencor Investigative Site | Recruiting | Houston | Texas | 77024 | United States |
| Xencor Investigative Site | Recruiting | Houston | Texas | 77090 | United States |
| Xencor Investigative Site | Recruiting | Kingwood | Texas | 77339 | United States |
| Xencor Investigative Site | Recruiting | Lubbock | Texas | 79424 | United States |
| Xencor Investigative Site | Recruiting | San Antonio | Texas | 78229 | United States |
| Xencor Investigative Site | Recruiting | Tyler | Texas | 75701 | United States |
| Xencor Investigative Site | Recruiting | Webster | Texas | 77598 | United States |
| Xencor Investigative Site | Recruiting | Richmond | Virginia | 23229 | United States |
| Xencor Investigative Site | Recruiting | Wollongong | New South Wales | 2500 | Australia |
| Xencor Investigative Site | Recruiting | South Brisbane | Queensland | 4101 | Australia |
| Xencor Investigative Site | Recruiting | Southport | Queensland | 4215 | Australia |
| Xencor Investigative Site | Completed | Joondalup | Western Australia | 6027 | Australia |
| Xencor Investigative Site | Completed | Nedlands | Western Australia | 6009 | Australia |
| Xencor Investigative Site | Recruiting | Sofia | 1618 | Bulgaria |
| Xencor Investigative Site | Recruiting | Vancouver | British Columbia | V6Z 2K5 | Canada |
| Xencor Investigative Site | Recruiting | London | Ontario | N6K 1M5 | Canada |
| Xencor Investigative Site | Recruiting | Scarborough Village | Ontario | M1S4T7 | Canada |
| Xencor Investigative Site | Recruiting | Montreal | Quebec | H3H 1EB | Canada |
| Xencor Investigative Site | Recruiting | Rijeka | 51000 | Croatia |
| Xencor Investigative Site | Recruiting | Zagreb | 10000 | Croatia |
| Xencor Investigative Site | Recruiting | Tbilisi | 0112 | Georgia |
| Xencor Investigative Site | Recruiting | Athens | Attica | 10676 | Greece |
| Xencor Investigative Site | Recruiting | Heraklion | Crete | 71500 | Greece |
| Xencor Investigative Site | Recruiting | Thessaloniki | 54642 | Greece |
| Xencor Investigative Site | Recruiting | Nyíregyháza | Szabolcs-Szatmár-Bereg | H-4405 | Hungary |
| Xencor Investigative Site | Recruiting | Budapest | 1136 | Hungary |
| Xencor Investigative Site | Recruiting | Budapest | 1139 | Hungary |
| Xencor Investigative Site | Recruiting | Vác | 2600 | Hungary |
| Xencor Investigative Site | Recruiting | Chisinau | Moldova |
| Xencor Investigative Site | Recruiting | Wroclaw | Lower Silesian Voivodeship | 53-611 | Poland |
| Xencor Investigative Site | Recruiting | Warsaw | Mazonian | 00-189 | Poland |
| Xencor Investigative Site | Recruiting | Sopot | Pomeranian Voivodeship | 81-756 | Poland |
| Xencor Investigative Site | Recruiting | Bydgoszcz | 85-079 | Poland |
| Xencor Investigative Site | Recruiting | Katowice | 40-748 | Poland |
| Xencor Investigative Site | Recruiting | Staszów | 28-200 | Poland |
| Xencor Investigative Site | Recruiting | Szczecin | 71-685 | Poland |
| Xencor Investigative Site | Recruiting | Warsaw | 004-501 | Poland |
| Xencor Investigative Site | Recruiting | Bucharest | District 1 | 01-1658 | Romania |
| Xencor Investigative Site | Recruiting | Cluj-Napoca | 400006 | Romania |
| Xencor Investigative Site | Recruiting | Lutsk | Volyn Oblast | 43005 | Ukraine |
| Xencor Investigative Site | Recruiting | Ivano-Frankivsk | 76008 | Ukraine |
| Xencor Investigative Site | Recruiting | Kyiv | 01135 | Ukraine |
| Xencor Investigative Site | Recruiting | Kyiv | 02091 | Ukraine |
| Xencor Investigative Site | Recruiting | Lviv | 79000 | Ukraine |
| Xencor Investigative Site | Recruiting | Lviv | 79010 | Ukraine |
| Xencor Investigative Site | Recruiting | Lviv | 79059 | Ukraine |
| Xencor Investigative Site | Recruiting | Uzhhorod | 88000 | Ukraine |
| Xencor Investigative Site | Recruiting | Vinnytsia | 21009 | Ukraine |
| Xencor Investigative Site | Recruiting | Vinnytsia | 21028 | Ukraine |
| Xencor Investigative Site | Recruiting | Zhytomyr | 10001 | Ukraine |
| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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